Lofepramine, sold under the brand names Gamanil, Lomont, and Tymelyt among others, is a tricyclic antidepressant (TCA) which is used to treat depression.[5][3][8] The TCAs are so named as they share the common property of having three rings in their chemical structure. Like most TCAs lofepramine is believed to work in relieving depression by increasing concentrations of the neurotransmitters norepinephrine and serotonin in the synapse, by inhibiting their reuptake.[5] It is usually considered a third-generation TCA, as unlike the first- and second-generation TCAs it is relatively safe in overdose and has milder and less frequent side effects.[9]

Lofepramine use during pregnancy is advised against unless the benefits clearly outweigh the risks.[5] This is because its safety during pregnancy has not been established and animal studies have shown some potential for harm if used during pregnancy.[5] If used during the third trimester of pregnancy it can cause insufficient breathing to meet oxygen requirements, agitation and withdrawal symptoms in the infant.[5] Likewise its use by breastfeeding women is advised against, except when the benefits clearly outweigh the risks, due to the fact it is excreted in the breast milk and may therefore adversely affect the infant.[5] Although the amount secreted in breast milk is likely too small to be harmful.[12]

Compared to other TCAs, lofepramine is considered to be less toxic in overdose.[12] Its treatment is mostly a matter of trying to reduce absorption of the drug, if possible, using gastric lavage and monitoring for adverse effects on the heart.[5]

Monoamine oxidase inhibitors (MAOIs). Advised not to be started until at least 2 weeks after stopping MAOIs. MAOIs are advised not to be started until at least 1–2 weeks after stopping TCAs like lofepramine.

Moclobemide. Moclobemide is advised not to be started until at least one week after treatment with TCAs is discontinued.

Nitrates. Could possibly reduce the effects of sublingual tablets of nitrates (failure to dissolve under tongue owing to dry mouth).

Lofepramine is extensively metabolized, via cleavage of the p-chlorophenacyl group, to the TCA, desipramine, in humans.[5][8][1] However, it is unlikely this property plays a substantial role in its overall effects as lofepramine exhibits lower toxicity and anticholinergicside effects relative to desipramine while retaining equivalent antidepressant efficacy.[8] The p-chlorophenacyl group is metabolized to p-chlorobenzoic acid which is then conjugated with glycine and excreted in the urine.[5] The desipramine metabolite is partly secreted in the faeces.[5] Other routes of metabolism include hydroxylation, glucuronidation, N-dealkylation and N-oxidation.[5][1]

Lofepramine was developed by Leo Läkemedel AB.[34] It first appeared in the literature in 1969 and was patented in 1970.[34] The drug was first introduced for the treatment of depression in either 1980 or 1983.[34][35]

^ abcdeRoth, BL; Driscol, J. "PDSP Ki Database". Psychoactive Drug Screening Program (PDSP). University of North Carolina at Chapel Hill and the United States National Institute of Mental Health. Retrieved 14 August 2017.